Published European Patent Application No. 154,142, and U.S. application Ser. No. 755,863, now abandoned, filed July 17, 1985 which are incorporated herein by reference, disclose the compound (2R,12bS)-N-(1,3,4,6,7,12-hexahydro-2H-benzo[b]furo[2,3-a]-quinolizin-2-yl )-N-methyl-2-hydroxyethanesulfonamide and the quinolizin-2-one intermediate and alternate routes for their synthesis. With the present invention there is provided a new enantioselective route for the synthesis of the intermediate.
The quinolizin-2-one intermediate was previously prepared by standard chemical resolution of racemic ketoamine with L-(+)di-p-toluoyl tartaric acid to give (-)12b(S)ketoamine in 30-35% yield. A resolution process has a maximum yield of 50%, thus one must always lose 50-65% of the total racemic material being resolved. The present invention produces 12b(S)ketoamine of greater than 90% optical purity, with optimization to 99% optical purity possible. This invention obviates the need for chemical resolution and, thus, provides a more efficient synthesis of the (-)-12b(S)ketoamine.